Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS4778896 A
Publication typeGrant
Application numberUS 07/086,418
Publication dateOct 18, 1988
Filing dateAug 17, 1987
Priority dateSep 4, 1986
Fee statusPaid
Also published asCA1302419C, DE3630046A1, EP0260485A1, EP0260485B1
Publication number07086418, 086418, US 4778896 A, US 4778896A, US-A-4778896, US4778896 A, US4778896A
InventorsBernd Gallenkamp
Original AssigneeBayer Aktiengesellschaft
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Process for the preparation of 5-chloromethylpyridines
US 4778896 A
Abstract
A process for the preparation of 5-chloromethylpyridines of the formula (I) ##STR1## in which R1 represents chlorine or nitro,
R2 represents chlorine, and
n represents the number 0 to 1, comprising chlorinating 5-methylpyridine of the formula (II) ##STR2## in which R1, R2 and n have the abovementioned meanings, at temperatures between 0 C. and 100 C., if appropriate in the presence of acid acceptors and if appropriate in the presence of inert diluents.
Images(4)
Previous page
Next page
Claims(7)
What is claimed is:
1. A process for the preparation of a 5-chloromethylpyridine of the formula (I) ##STR11## in which R1 represents chlorine or nitro,
R2 represents chlorine, and
n represents the number 0 or 1, comprising chlorinating a 5-methylpyridine of the formula ##STR12## in which R1, R2 and n have the abovementioned meanings, at temperatures between 0 C. and 100 C. in the presence of an acid acceptor selected from the group consisting of an alkali metal carbonate, an aliphatic amine, an aromatic amine, and a heterocyclic amine and in the presence of an inert diluent, the resultant reaction mixture being stirred for several hours.
2. A process according to claim 1, wherein the acid acceptor is selected from the group consisting of sodium carbonate; potassium carbonate; triethylamine; trimethylamine; dimethylaniline; dimethylbenzylamide; pyridine; 1,5-diazabicyclo-[4,3,0]-non-5-ene; 1,8-diazabicyclo-[5,4,0]-undec-7-ene and 1,4-diazabicyclo-[2,2,2]-octane.
3. A process according to claim 1, wherein the inert diluent is selected from the group consisting of an aliphatic hydrocarbon halogenated aliphatic hydrocarbon and an ether.
4. A process according to claim 3, wherein the inert diluent is a halogenated aliphatic hydrocarbon.
5. A process according to claim 1, wherein the diluent is selected from the group consisting of methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, diethyl ether, dibutyl ether, methyl tert.-butyl ether, glycol dimethyl ether, diglycol dimethyl ether, tetrahydrofuran and dioxane.
6. A process according to claim 1, wherein the chlorination is carried out at temperatures between 40 C. and 80 C.
7. A process according to claim 1, wherein the 5-chloromethylpyridine is 2-chloro-5chloromethylpyridine.
Description

The present invention relates to a new process for the preparation of 5-chloromethylpyridines, which can be used, for example, as intermediates for the preparation of insecticides.

It is already known that 5-chloromethylpyridines can be obtained by reacting 5-hydroxymethylpyridines with chlorinating agents, such as, for example, thionyl chloride (cf. EP-OS (European Published Specification) No. 163,855 and J. Het. Chem. 16, 333 (1979)). This process has the disadvantage that many reaction stages are necessary for the preparation of 5-chloromethylpyridines.

It is furthermore known that direct chlorination of the methyl group of 3-methylpyridines is not possible (cf. Helv. Chim. Acta 59, 179 ff (1976) and Angew. Chem. 1963, 236 ff).

It has now been found that 5-chloromethylpyridines of the general formula (I) ##STR3## in which R1 represents chlorine or nitro,

R2 represents chlorine, and

n represents the number 0 or 1,

are obtained when 5-methylpyridines of the formula (II) ##STR4## in which R1, R2 and n have the abovementioned meanings, are chlorinated at temperatures between 0 C. and 100 C., if appropriate in the presence of acid acceptors and if appropriate in the presence of inert diluents.

Surprisingly, the process according to the invention can successfully be used to prepare 5-chloromethylpyridines in a simple fashion and at low expense by direct chlorination of corresponding 5-methylpyridines. According to the state of the art, 4 complicated reaction stages are necessary for the preparation of 5-chloromethylpyridines: ##STR5## (cf. J. Org. Chem. 34, 3545 (1969) and J. Het. Chem. 16, 333 (1979)). This problematic reaction sequence can now be avoided in a surprisingly simple fashion.

The process according to the invention is preferred for preparing the following compounds of the formula (I): 2-chloro-, 2,3-dichloro-, 4-chloro , 2,4-dichloro- and 2-nitro-5-chloromethylpyridine.

The process according to the invention is particularly preferred for preparing the following compound of the formula (I): 2-chloro-5-chloromethylpyridine.

If 2-chloro-5-methyl-pyridine and elemental chlorine are used as starting materials in the process according to the invention, the reaction can be represented by the following equation: ##STR6##

Formula (II) provides a general definition of the 5-methylpyridines to be used as starting materials for the process according to the invention. In this formula, R1 and R2 preferably represent those radicals which are given above as being preferred or as being particularly preferred in the context of the definition of the substituents in the formula (I).

Examples of compounds of the formula (II) which may be mentioned are: 2-chloro-, 2,3-dichloro-, 4-chloro-, 2,4-dichloro- and 2-nitro-5-methylpyridine.

The compounds of the formula (II) are known or can be prepared in an analogous fashion by known processes.

The process, according to the invention, for the preparation of compounds of the formula (I) is preferably carried out using diluents. Suitable diluents in this process are virtually all inert organic solvents. These include, preferably, aliphatic, optionally halogenated hydrocarbons, such as methylene chloride, ethylene chloride, chloroform and carbon tetrachloride, ethers, such as diethyl and dibutyl ether, methyl tert.-butyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane.

The process according to the invention is preferably carried out in the presence of acid acceptors. Acid acceptors which can be employed in the process according to the invention are all acid-binding agents which can conventionally be used for such reactions Preferably suitable are alkali metal carbonates, such as sodium carbonate and potassium carbonate, furthermore aliphatic, aromatic or heterocyclic amines, for example triethylamine, trimethylamine, dimethylaniline, dimethylbenzylamine, pyridine, 1,5-diazabicyclo-[4,3,0]-non-5-ene (DBN), 1,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) and 1,4-diazabicyclo-[2,2,2]-octane (DABCO).

The reaction temperatures can be varied within a relatively wide range in the process according to the invention. In general, the process is carried out at temperatures between 0 C. and 100 C. , preferably at temperatures between 40 C. and 80 C. . The process according to the invention is generally carried out under atmospheric pressure.

To carry out the process according to the invention in a preferred manner, elemental chlorine is passed through a mixture of starting material of the formula (II), acid acceptor and diluent, and the reaction mixture is stirred for several hours at the temperature necessary in each case (preferably in the range 40 to 80 C. ). Work-up is effected by generally conventional methods.

The 5-chloromethylpyridines to be prepared by the process according to the invention can be employed, for example, as intermediates for the preparation of nitromethylene derivatives which are effective as insecticides (cf. EP-A No. 163,855).

In this connection, the following further processing equation may be shown as an example: ##STR7##

PREPARATION EXAMPLE ##STR8##

Elemental chlorine is passed through a solution of 2.54 g (0.02 mol) of 2-chloro-5-methylpyridine and 4 g (0.0265 mol) of sodium carbonate in 10 ml of carbon tetrachloride at 60 C. . The course of the reaction is followed by gas chromatography. After 10 hours, the reaction mixture is cooled and concentrated.

2.1 g (65% of theory) of 2-chloro-5-chloromethylpyridine are obtained. The structure is confirmed by 1 H NMR spectra.

1 NMR (CDCl3): δ=8.4 (d, 1H, --CH--N═), 7.73 (dd,1H, ##STR9## 7.35 (d, 1H, ##STR10## 4.57 (s, 2H, --CH2) ppm.

It will be appreciated that the instant specification and claims are set forth by way of illustration and not limitation, and that various modifications and changes may be made without departing from the spirit and scope of the present invention.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3123608 *Nov 8, 1961Mar 3, 1964 Process for chlorination of side chains
US3931200 *Jan 22, 1974Jan 6, 1976The Dow Chemical CompanySubstituted pyridinylalkoxy-, pyridinylalkylsulfonyl- and pyridinylalkylthio- phenylureas
US4205175 *Feb 7, 1979May 27, 1980Imperial Chemical Industries LimitedChlorination process
EP0163855A1 *Apr 9, 1985Dec 11, 1985Nihon Tokushu Noyaku Seizo K.K.Nitromethylene derivatives, intermediates, and process for their preparation as insecticides
Non-Patent Citations
Reference
1 *F. E. Ziegler and J. G. Sweeny, J. Org. Chem., 34, 3545 3548, (1969).
2F. E. Ziegler and J. G. Sweeny, J. Org. Chem., 34, 3545-3548, (1969).
3 *H. Fritz, C. D. Weis and T. Winkler, Helv. Chim. Acta, 59, 170 190, (1976).
4H. Fritz, C. D. Weis and T. Winkler, Helv. Chim. Acta, 59, 170-190, (1976).
5 *J. W. Tilley, P. Levitan and R. W. Kierstead, J. Het. Chem., 16, 333 337, (1979).
6J. W. Tilley, P. Levitan and R. W. Kierstead, J. Het. Chem., 16, 333-337, (1979).
7 *Synthesis, Nr. 8, Aug. 1984, Seiten 676 679; G. R. Newkome et al: Alpha methyl functionalization of electron poor heterocycles: free radical chlorination .
8Synthesis, Nr. 8, Aug. 1984, Seiten 676-679; G. R. Newkome et al: "Alpha-methyl functionalization of electron-poor heterocycles: free radical chlorination".
9 *W. Mathes and H. Schuly, Angew. Chem., 235 240, (1963).
10W. Mathes and H. Schuly, Angew. Chem., 235-240, (1963).
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US5103011 *Jan 23, 1991Apr 7, 1992Bayer AktiengesellschaftPreparation of 2-chloro-5- methyl-pyridine
US5198549 *May 13, 1991Mar 30, 1993Bayer AktiengesellschaftSide-chain chlorination of alkylated nitrogen heteroaromatics
US5324841 *Feb 24, 1993Jun 28, 1994Central Glass CompanyMethod of chlorinating side chain of 2-chloro-methylpyridine
US5508410 *Nov 30, 1993Apr 16, 1996Reilly Industries, Inc.Process for preparing 2-halo-5-substituted pyridines
US5521316 *May 20, 1994May 28, 1996Cytec Technology Corp.Chloroalkyl pyridinum hydrochloride compounds and processes for their preparation
US5623076 *Dec 18, 1995Apr 22, 1997Bayer AktiengesellschaftProcess for the preparation of chloromethylpyridines
US5686619 *Mar 6, 1995Nov 11, 1997Cytec Technology Corp.Chloroalkyl pyridinium hydrochloride compounds and processes for their preparation
US6022974 *May 11, 1993Feb 8, 2000Lonza Ltd.Process for the production of 2-chloro-5-chloromethyl-pyridine
US6150528 *Mar 2, 1998Nov 21, 2000Bayer AktiengesellschaftMethod for producing 5-aminomethyl-2-chloropyridines
US8138350Jul 7, 2007Mar 20, 2012Bayer Cropscience AgN′-cyano-N-halogenalkylimidamide derivatives
US8343893Jun 17, 2010Jan 1, 2013Bayer Cropscience AgSubstituted enaminocarbonyl compounds
US8487112Sep 5, 2008Jul 16, 2013Bayer Cropscience AgMethod for producing 4-aminobut-2-enolides
US8563584Mar 25, 2009Oct 22, 2013Bayer Cropscience AgSubstituted enaminothiocarbonyl compounds
US20100048646 *Jul 7, 2007Feb 25, 2010Bayer Cropscience AgN'-Cyano-N-Halogenalkylimidamide Derivatives
US20100204480 *Sep 5, 2008Aug 12, 2010Bayer CropscienceMethod for producing 4-aminobut-2-enolides
US20100324103 *Jun 17, 2010Dec 23, 2010Bayer Cropscience AgSubstituted Enaminocarbonyl Compounds
US20110039894 *Mar 25, 2009Feb 17, 2011Bayer Cropscience AgSubstituted enaminothiocarbonyl compounds
CN102796039A *Aug 16, 2012Nov 28, 2012浙江工业大学Method for continuous preparation of 2-chloro-5-chloromethylpyridine in microchannel
CN102796039B *Aug 16, 2012Nov 12, 2014浙江工业大学Method for continuous preparation of 2-chloro-5-chloromethylpyridine in microchannel
Classifications
U.S. Classification546/304, 546/345, 546/346
International ClassificationC07D213/61, C07D213/26
Cooperative ClassificationC07D213/26, C07D213/61
European ClassificationC07D213/26, C07D213/61
Legal Events
DateCodeEventDescription
Aug 17, 1987ASAssignment
Owner name: BAYER AKTIENGESELLSCHAFT, LEVERKUSEN, GERMANY A CO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:GALLENKAMP, BERND;REEL/FRAME:004775/0942
Effective date: 19870807
Owner name: BAYER AKTIENGESELLSCHAFT,GERMANY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GALLENKAMP, BERND;REEL/FRAME:004775/0942
Effective date: 19870807
Jun 20, 1989CCCertificate of correction
Nov 18, 1991FPAYFee payment
Year of fee payment: 4
Mar 14, 1996FPAYFee payment
Year of fee payment: 8
Mar 20, 2000FPAYFee payment
Year of fee payment: 12